Camptothecin derivatives and the use thereof as antitumor agents

Camptothecin derivatives having antitumor activity

Retinoid derivatives with antiangiogenic, antitumoral and proapoptotic activities

Described and claimed are compounds of Formula (I) in which R, R', R'', A, and D have the meanings described in the text, as useful agents in the cure of pathologies characterized by altered angiogenesis and as antitumorals.

Derivatives of partially desulphated glycosaminoglycans endowed with antiangiogenic activity and devoid of anticoagulating effect

Partially desulfated glycosaminoglycan derivatives are described, particularly heparin, and more particularly formula (I) compounds where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives exhibit antiangiogenic activity and are devoid of anticoagulant activity.

Derivatives of partially desulphated glycosaminoglycans endowed with antiangiogenic activity and devoid of anticoagulating effect

Derivatives of partially desulphated glycosaminoglycans as heparanase inhibitors, endowed with antiangiogenic activity and devoid of anticoagulating effect

Partially desulphated glycosaminoglycan derivatives are described, particularly heparin, and more particularly a compound of formula (I) where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives have antiangiogenic and heparanase-inhibiting activity and are devoid of anticoagulant activity.

Biphenyl and Naphthyl-Phenyl Hydroxamic Acid Derivatives

Biphenyl and phenyl-naphthyl compounds bearing a hydroxamic group, which are endowed with antitumour, and anti-angiogenic activity These compounds are therefore particularly useful for the treatment of drug-resistant tumours.

Camptothecin derivatives having antitumor activity

Camptothecin derivatives of camptothecin of formula (I):wherein the groups R1, R2 and R3 are as defined in the description are disclosed.The compounds of formula (I) are endowed with antitumor activity and show a good therapeutic index.Processes for the preparation of the compounds of formula (I) and their use in the preparation of medicaments useful in the treatment of tumors, viral infections and antiplasmodium falciparum are also disclosed.

Biphenyl and Naphthyl-Phenyl Hydroxamic Acid Derivatives

Biphenyl and phenyl-naphthyl compounds bearing a hydroxamic group, which are endowed with antitumor, and anti-angiogenic activity These compounds are therefore particularly useful for the treatment of drug-resistant tumors.

Industrial process for the production of L-carnitine

The present invention describes a process for the industrial production of L-carnitine, comprising the enantioselective reduction of an alkyl 4-chloro-3-oxobutyrate or 4-chloro-3-oxobutyramide. The optically active 3-hydroxy derivative thus obtained is reacted with trimethylamine, obtaining crude L-carnitine, which is then finally purified. The catalyst used for the reduction is a complex of ruthenium bound to a penta-atomic bis-heteroaromatic system. The reduction reaction, performed in controlled conditions of hydrogen pressure, substrate concentration, temperature, and substrate: catalyst molar ratio, enables 4-chloro-3-hydoxybutyrate or 4-chloro-hydroxybutyamide to be obtained in a high yield. The process described, which leads to L-carnitine being obtained, is easily applicable on an industrial scale.

Camptothecin derivatives having antitumor activity

Camptothecin derivatives of camptothecin of formula (I) exhibit antitumor activity and show a good therapeutic index and are used in the treatment of tumors, viral infections and antiplasmodium falciparum.

Derivatives of partially desulphated glycosaminoglycans endowed with antiangiogenic activity and devoid of anticoagulating effect

Partially desulfated glycosaminoglycan derivatives are described, particularly heparin, and more particularly formula (I) compounds where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives exhibit antiangiogenic activity and are devoid of anticoagulant activity.

Methods for inhibiting the growth of tumors with 7-substituted camptothecin derivatives

Compounds of formula (I), wherein: R1 is -CN, -CH(CN)-R4, -CH=C(CN)-R4, -CH2-CH(CN)-R4, -C(=NOH)-NH2, -C(=NH)-NH2, -CH=C(NO2)-R4, -CH(CN)-R5, -CH(CH2NO2)-R5; 5-tetrazolyl, 2-(4,5-dihydrooxazolyl), 1,2,4-oxadiazolin-3-yl-5-one; R2 is hydrogen; R3 is hydrogen, OR6; R4 is hydrogen, C1-C6 linear or branched alkyl, CN, COOR7; R5 is hydrogen, OR8; R6 is hydrogen, C1-C6 linear or branched alkyl, (C6-C12) aryl (C1-C4) alkyl, (C1-C4) alkoxy (C1-C4) alkyl, (C1-C4) alkyl (C6-C12) aryl, (C6-C12) aryl (C2-C4) acyl, (C2-C4) acyl, amino (C1-C4) alkyl, amino (C2-C4) acyl, glycosyl; R7 is hydrogen, C1-C6 linear or branched alkyl, (C6-C12) aryl (C1-C4) alkyl, (C1-C4) alkoxy (C1-C4) alkyl, (C1-C4) alkyl (C6-C12) aryl; R8 has the same meanings of R6, independently of the latter. These compounds are active as topoisomerase I inhibitors and can be used as antitumor drugs.

Derivatives of partially desulphated glycosaminoglycans as heparanase inhibitors, endowed with antiangiogenic activity and devoid of anticoagulating effect

Partially desulphated glycosaminoglycan derivatives are described, particularly heparin, and more particularly formula (I) compounds where the U, R and R1 groups have the meanings indicated in the description. Said glycosaminoglycan derivatives are endowed with antiangiogenic and heparanase-inhibiting activity ans are devoid of anticoagulant activity.

Bis-heterocyclic compounds with antitumour and chemosensitising activity

Bis-heterocyclic compounds of general formula (I) are described which are useful as antitumour and chemosensitising agents.

Camptothecins conjugated in position 7 to cyclic peptides as cytostatic agents

Compounds of Formula (I) are described in which the R1 group is as defined in the specification and includes the condensation of the camptothecin molecule in position 7 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors v3 and v5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

7-Imino derivatives of camptothecin having antitumor activity

Camptothecin derivatives of camptothecin of formula (I) wherein the groups R1, R2 and R3 are as defined in the description are disclosed. The compounds of formula (I) are endowed with antitumor activity and show a good therapeutic index. Processes for the preparation of the compounds of formula (I) and their use in the preparation of medicaments useful in the treatment of tumors, viral infections and antiplasmodium falciparum are also disclosed.

Cyclopeptide derivatives with anti-integrin activity

Formula (I) compounds are described c(R1-Arg-Gly-Asp-R2) where the meanings of the various groups are as described here below, which are integrin inhibitors, and particularly inhibitors of integrins of the α,β3 and α,β5 family, and therefore are useful as medicaments, particularly for the treatment of the diseases underlying abnormal angiogenesis, such as retinopathy, acute renal failure, osteoporosis and metastases. The compounds described herein, when suitably labelled, are also useful as diagnostic agents, especially for the detection of small tumour masses and arterial occlusion events, and as targeted drug vectors.

Derivatives of partially desulphated glycosaminoglycans as heparanase inhibitors, endowed with antiangiogenic activity and devoid of anticoagulating effect

Partially desulphated glycosaminoglycan derivatives are described, particularly heparin, and more particularly a compound of formula (I) where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives have antiangiogenic and heparanase-inhibiting activity and are devoid of anticoagulant activity.

Derivatives of partially desulphated glycosaminoglycans as heparanase inhibitors, endowed with antiangiogenic activity and devoid of anticoagulating effect

Partially desulphated glycosaminoglycan derivatives are described, particularly heparin, and more particularly a compound of formula (I) where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives have antiangiogenic and heparanase-inhibiting activity and are devoid of anticoagulant activity.

Retinoid derivatives with antiangiogenic, antitumoral and proapoptotic activities

Are described compounds of Formula (I) in which R, R, R, A, and D have the meanings described in the text, as useful agents in the cure of pathologies characterized by altered angiogenesis and as antitumorals.

Bis-heterocyclic compounds with antitumour and chemosensitising activity

Bis-heterocyclic compounds of general formula (I) are described which are useful as antitumour and cheomsensitising agents.

Derivatives of partially desulphated glycosaminoglycans endowed with antiangiogenic activity and devoid of anticoagulating effect

Partially desulfated glycosaminoglycan derivatives are described, particularly heparin, and more particularly formula (I) compounds where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives exhibit antiangiogenic activity and are devoid of anticoagulant activity.

Use of natural chrysanthone compounds having antiangiogenic activity

A series of compounds of natural origin are described, as useful agents for the treatment of diseases characterised by abnormal angiogenesis. These compounds are: chrysanthone A having formula (I); chrysanthone B having formula (II); and chrysanthone C having formula (III).

Camptothecin derivatives having antitumor activity

Camptothecin derivatives of camptothecin of formula (I) wherein the groups R1, R2and R3are as defined in the description are disclosed. The compounds of formula (I) are endowed with antitumor activity and show a good therapeutic index. Processes for the preparation of the compounds of formula (I) and their use in the preparation of medicaments useful in the treatment of tumors, viral infections and antiplasmodium falciparum are also disclosed.

Derivatives of partially desulphated glycosaminoglycans as heparanase inhibitors, endowed with antiangiogenic activity and devoid of anticoagulating effect

Partially desulphated glycosaminoglycan derivatives are described, particularly heparin, and more particularly a compound of formula (I) where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives have antiangiogenic and heparanase-inhibiting activity and are devoid of anticoagulant activity.

7-t-butoxyiminomethylcamptothecin conjugated in position 20 with integrin antagonists

Compounds of Formula (I) are described: in which the R1 group is as defined in the specification and includes the condensation of 7-t-butoxyiminomethylcamptothecin in position 20 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors alphavbeta3 and alphavbeta5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

7-imino derivatives of camptothecin having antitumor activity

Camptothecin derivatives of camptothecin of formula (I) wherein the groups R 1 , R 2 and R 3 are as defined in the description are disclosed. The compounds of formula (I) are endowed with antitumor activity and show a good therapeutic index. Processes for the preparation of the compounds of formula (I) and their use in the preparation of medicaments useful in the treatment of tumors, viral infections and antiplasmodium falciparum are also disclosed.

Industrial process for the production of L-carnitine

The present invention describes a process for the industrial production of L-carnitine, comprising the enantioselective reduction of an alkyl 4-chloro-3-oxobutyrate or 4-chloro-3-oxobutyramide. The optically active 3-hydroxy derivative thus obtained is reacted with trimethylamine, obtaining crude L-carnitine, which is then finally purified. The catalyst used for the reduction is a complex of ruthenium bound to a penta-atomic bis-heteroaromatic system. The reduction reaction, performed in controlled conditions of hydrogen pressure, substrate concentration, temperature, and substrate: catalyst molar ratio, enables 4-chloro-3-hydoxybutyrate or 4-chloro-hydroxybutyamide to be obtained in a high yield. The process described, which leads to L-carnitine being obtained, is easily applicable on an industrial scale.

Camptothecin derivatives having antitumor activity

Camptothecin derivatives of camptothecin of formula (I) exhibit antitumor activity and show a good therapeutic index and are used in the treatment of tumors, viral infections and antiplasmodium falciparum.

Derivatives of partially desulphated glycosaminoglycans as heparanase inhibitors, endowed with antiangiogenic activity and devoid of anticoagulating effect

Partially desulphated glycosaminoglycan derivatives are described, particularly heparin, and more particularly a compound of formula (I) where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives have antiangiogenic and heparanase-inhibiting activity and are devoid of anticoagulant activity.

Bis-heterocyclic compounds with antitumour and chemosensitising activity

Bis-heterocyclic compounds of general formula (1) are described which are useful as antitumour and cheomsensitising agents.

Camptothecin derivatives having antitumor activity

Camptothecin derivatives of camptothecin of formula (I)wherein the groups R1, R2 and R3 are as defined in the description are disclosed.The compounds of formula (I) are endowed with antitumor activity and show a good therapeutic index.Processes for the preparation of the compounds of formula (I) and their use in the preparation of medicaments useful in the treatment of tumors, viral infections and antiplasmodium falciparum are also disclosed.

Camptothecin Derivatives Conjugated in Position 20 with Integrin Antagonists

Compounds or formula (I) are described, in which the R and R1 groups are as defined here below and include the condensation of the camptothecin molecule in position 20 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors αvβ3 and αvβ5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

Camptothecins Conjugated in Position 7 to Cyclic Peptides as Cytostatic Agents

Compounds of Formula (I) are described in which the R1 group is as defined in the specification and includes the condensation of the camptothecin molecule in position 7 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors αvβ3 and αvβ5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

NOVEL DUAL TARGETING ANTITUMORAL CONJUGATES

The present invention relates to dual-targeting cytotoxic compounds of formula (I) and to their preparation. The described compounds are endowed with tumour specific action, incorporating three functional units: a tumour recognition moiety and a tumour selective enzymatic substrate sequence connected together by means of a spacer. These conjugates are designed to guarantee serum stability and, at the same time, the desired action inside the tumour cells as a result of enzymatic cleavability. [(L-D)nE]m-F-D-PI-SI-CT Formula (I).

DERIVATIVES OF PARTIALLY DESULPHATED GLYCOSAMINOGLYCANS ENDOWED WITH ANTIANGIOGENIC ACTIVITY AND DEVOID OF ANTICOAGULATING EFFECT

Partially desulfated glycosaminoglycan derivatives are described, particularly heparin, and more particularly formula (I) compounds where the U, R and R1 groups have the meanings indicated in the description. These glycosaminoglycan derivatives exhibit antiangiogenic activity and are devoid of anticoagulant activity.

7-Polyaminoalkyl(oxy)iminomethylcamptothecins bearing protective groups

Compounds are disclosed with the general formula in which the groups are as defined in the description here below and characterized by the presence of polyamine substituents on the imine/oxime residue, such amine groups being in turn protected by suitable protective groups. Said compounds are endowed with potent topoisomerase I inhibiting activity and therefore are useful as medicaments for the treatment of tumors and viral and parasite infections.

7-T-Butoxyiminomethylcamptothecin Conjugated in Position 20 With Integrin Antagonists

Compounds of Formula (I) are described: in which the R1 group is as defined in the specification and includes the condensation of 7-t-butoxyiminomethylcamptothecin in position 20 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors αvβ3 and αvβ5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

7-Polyaminoalkyl(oxy)iminomethylcamptothecins bearing protective groups

Compounds are disclosed with the general formula in which the groups are as defined in the description here below and characterized by the presence of polyamine substituents on the imine/oxime residue, such amine groups being in turn protected by suitable protective groups. Said compounds are endowed with potent topoisomerase I inhibiting activity and therefore are useful as medicaments for the treatment of tumours and viral and parasite infections.

Retinoid Derivatives With Antiangiogenic, Antitumoral And Proapoptotic Activities

Described and claimed are compounds of Formula (I) in which R, R′, R″, A, and D have the meanings described in the text, as useful agents in the cure of pathologies characterized by altered angiogenesis and as antitumorals.

Substituted indolylmethylene-oxindole analogues as tyrosine kinase inhibitors

Indol-3-ylmethylene-2-oxindole derivatives having general formula (I), wherein one or two of R, R1, R2 and R3 are a substituent selected independently from: a) a -X-(CH2)m-NH2, -X-(CH2)m-NR4R5, or -X-(CH2)m-NHR6 group, b) a -NHC(NH)NH2, -NHC(NH)NR4R5, -NHC(NH)NHR6, -N=CH-NHz, -N=CH-NR4R5 or -N=CH-NHR6 group, c) a -X-(CH2)m-COR7 group, d) a -CORa or COR8 group, e) a -Y-CO-Y'-R9 group, f) a -NHR6 or -NHR10 group, and the pharmaceutically acceptable salts of salt forming compounds of formula (I), have tyrosine kinase inhibiting activity.

Poly-4-aminopyrrole-2-carboxamido derivatives and their use as antiuiral or antitumor agents

Compound of the formula (I) ##STR1## wherein n is zero or an integer of 1 to 3; R is (a) --NHR 3 , wherein R 3 is (a') --CON(NO)R 4 , in which R 4 is C 1 -C 4 alkyl either unsubstituted or substituted by halogen; or (b') --CO(CH 2 ) m --R 5 , in which R 5 is halogen, oxiranyl, methyloxiranyl, aziridinyl, a group ##STR2## or a group ##STR3## and m is zero or an integer of 1 to 4; or (b) ##STR4## wherein either R 6 and R 7 are the same and are each oxiranemethyl, aziridinemethyl, or C 2 -C 4 alkyl 2-substituted by halogen or by a group --OSO 2 R 8 wherein R 8 is C 1 -C 4 alkyl or phenyl, or one of R 6 and R 7 is hydrogen and the other is as defined above; each group R 1 is, independently, hydrogen or C 1 -C 4 alkyl; R 2 is a C 1 -C 6 alkyl group terminating with (i) a basic moiety chosen from an amino group, a mono- or di- C 1 -C 6 alkylamino group, an amidino group, a group ##STR5## imidazolyl, imidazolinyl, tetrahydropyrimidinyl and oxazolidinyl; or (ii) a carboxy group; or (iii) a free hydroxy group --OH or a glycosilated hydroxy group --OD wherein D is a glucose, mannose or ribose sugar residue or the daunosamine amino-sugar residue; with the proviso that n is different from one when R 2 is ##STR6## and the pharmaceutically acceptable salts thereof. The compounds are useful as antiviral and antitumor agents.

Site specific alkylating agents

The invention relates to distamycin A analogs of the following formula ##STR1## wherein n is 2, 3 or 4; A is an optionally substituted divalent radical chosen from ##STR2## and -Het- wherein Het is a pentatomic or hexatomic heteromonocyclic ring, except pyrrole; and wherein either one of R 1 and R 2 is hydrogen and the other is an acylating moiety or R 1 and R 2 are both hydrogen or both alkyl groups optionally substituted, including the pharmaceutically acceptable salts of the said compounds. The compounds of the invention can be useful antitumor and antiviral agents.

Site specific alkylating agents

The invention relates to distamycin A analogs of the following formula ##STR1## wherein n is 2, 3 or 4; A is an optionally substituted divalent radical chosen from ##STR2## and -Het- wherein Het is a pentatomic or hexatomic heteromonocyclic ring, except pyrrole; and wherein either one of R 1 and R 2 is hydrogen and the other is an acylating moiety or R 1 and R 2 are both hydrogen or both alkyl groups optionally substituted, including the pharmaceutically acceptable salts of the said compounds. The compounds of the invention can be useful antitumor and antiviral agents.

Site specific alkylating agents

The invention relates to distamycin A analogs of the following formula ##STR1## wherein n is 2, 3 or 4; A is an optionally substituted divalent radical chosen from ##STR2## and --Het-- wherein Het is a pentatomic or hexatomic heteromonocyclic ring, except pyrrole; and wherein either one of R 1 and R 2 is hydrogen and the other is an acylating moiety or R 1 and R 2 are both hydrogen or both alkyl groups optionally substituted, including the pharmaceutically acceptable salts of the said compounds. The compounds of the invention can be useful antitumor and antiviral agents.

Process for preparing 4-demethoxydaunomycinone

Daunomycins, process for their uses and intermediates

The known antibiotic daunomycin, and the novel compounds daunomycin-β-anomer and 4'-epidaunomycin (both α- and β-anomers) are prepared by condensing daunomycinone with reactive novel intermediates which are 1-chloro-2,3,6-trideoxy-3-trifluoroacetamido-4-trifluoroacetoxy-α-L-lyxo (or arabino) hexopyranoses.

New morpholino derivatives of daunorubicin and doxorubicin

Industrial process for the production of l-carnitine

The present invention describes a process for the industrial production of L-carnitine, comprising the enantioselective reduction of an alkyl 4-chloro-3-oxobutyrate or 4-chloro-3-oxobutyramide. The optically active 3-hydroxy derivative thus obtained is reacted with trimethylamine, obtaining crude L-carnitine, which is then finally purified. The catalyst used for the reduction is a complex of ruthenium bound to a penta-atomic bis-heteroaromatic system. The reduction reaction, performed in controlled conditions of hydrogen pressure, substrate concentration, temperature, and substrate: catalyst molar ratio, enables 4-chloro-3-hydroxybutyrate or 4-chloro-hydroxybutyramide to be obtained in a high yield. The process described, which leads to L-carnitine being obtained, is easily applicable on an industrial scale.

INDUSTRIAL PROCESS FOR THE PRODUCTION OF L-CARNITINA.

Morpholine derivatives of daunorubucyn and doxorubicyn

The invention relates to antitumour glycosides of anthracyclines having the formula and to methods for their preparations. The compounds possess valuable pharmacological properties and find application as medicaments. The invention also relates to the compositions containing these compounds as active ingredients, and to the application of the compounds.

NEW ANTHRACYCLINE SUBSTITUTES FOR USE AS ANTITUMOR DRUG

L'INVENTION A POUR OBJET DE NOUVEAUX GLYCOSIDES DE LA SERIE DES ANTHRACYCLINES ET UN PROCEDE POUR LES PREPARER. CES COMPOSES ONT LA FORMULE GENERALE SUIVANTE: (CF DESSIN DANS BOPI) AVEC LA CONDITION QUE: A.QUAND R REPRESENTE LE GROUPE -COCH OU -COCHOH, R EST -OH, R EST -OCH ET R EST H; B.QUAND R REPRESENTE LE GROUPE -COCH OU -COCHOH, R EST -OH, R EST H ET R EST -OCH. CES COMPOSES ONT UNE ACTIVITE ANTIMITOTIQUE QUI LES REND UTILISABLES COMME MEDICAMENT CONTRE LES TUMEURS MALIGNES.

4'-HALO-ANTHRACYCLINE GLYCOSIDES, PROCESS FOR THEIR PREPARATION AND THEIR USE AS A MEDICAMENT

ANTHRACYCLINES FOR TREATMENT OF TUMORS IN MEN

L'invention a pour objet des dérivés de daunorubicine d'un type nouveau. Ils répondent à la formule générale 1 : The invention relates to daunorubicin derivatives of a new type. They answer the general formula 1:

ANTHRACYCLINE GLYCOSIDES WITH ANTI-TUMOR ACTIVITY, THEIR PREPARATION, THE INTERMEDIATE COMPOUNDS OF THIS PREPARATION AND COMPOSITIONS AND THE USE THEREOF

NOUVEAUX ANTHRACYCLINE GLYCOSIDES DE FORMULE : (CF DESSIN DANS BOPI) OU R REPRESENTE HYDROGENE OU HYDROXY ET SOIT R SOIT R REPRESENTE HYDROGENE, L'AUTRE ETANT AMINOMETHYLE. LES NOUVEAUX COMPOSES ET LEURS SELS D'ADDITION PHARMACEUTIQUEMENT ACCEPTABLES SONT UTILES COMME AGENTS ANTITUMORAUX. NEW ANTHRACYCLINE GLYCOSIDES OF THE FORMULA: (CF DRAWING IN BOPI) OR R REPRESENTS HYDROGEN OR HYDROXY AND EITHER R OR R REPRESENTS HYDROGEN, THE OTHER IS AMINOMETHYL. THE NEW COMPOUNDS AND THEIR PHARMACEUTICALLY ACCEPTABLE ADDITIONAL SALTS ARE USEFUL AS ANTITUMOR AGENTS.

6-DEOXYANTHRACYCLINES AND PROCESS FOR PREPARING THEM

ANALOGUES DISACCHARIDES OF ANTITUMOR ANTHRACYCLINE AND METHOD FOR PREPARING THEM

L'invention a pour objet des dérivés disaccharides d'anthracycline. Ils ont la structure générale donnée par la formule I suivante : The subject of the invention is disaccharide derivatives of anthracycline. They have the general structure given by the following formula I:

PROCESS FOR PREPARING (14-14C) DAUNORUBICIN AND (14-14C) DOXORUBICIN

La présente invention a pour objet le procédé de préparation de la Ø14-**14Cõdaunorobucine et de la Ø14-**14Cõdoxorubicine. Ce procédé est caractérisé en ce que l'on fait réagir la 9-déacétyl-9-formyl-N-trifluoroacétyl-daunorubicine, en solution dans un solvant organique aprotique tel que CH2 Cl 2 ou l'éther diéthylique, à la température ambiante, pendant 60 mn environ sous vide, avec le Ø14Cõ-diazométhane pour former la Ø14-**14Cõ-N-trifluoroacétyl-daunorubicine, que l'on purifie par chromatographie sur colonne, ou sur plaque, de silica-gel, puis traite par une solution aqueuse à 0,1N de NaOH, ou de NH4 OH, une température de 0 à 5 degrés C pendant 30 à 60 mn environ, afin d'hydrolyser le groupement protecteur N-trifluoroacétyle et obtenir la Ø14-**14Cõ-daunorubicine sous forme de base libre qu'après traitement par la quantité stoechiométrique de HCI méthanolique, on isole sous forme de son chlorhydrate et, le cas échéant, fait réagir avec le brome pour donner le dérivé 4-bromo correspondant à partir duquel, par une hydrolyse de 100h à température ambiante au moyen d'une solution aqueuse de formiate de sodium, on obtient la Ø14-**14Cõ-doxorubicine qu'on isole finalement sous forme de son chlorhydrate. Elle se rapporte à un tel procédé de préparation. The present invention relates to the process for the preparation of Ø14 - ** 14Cõdaunorobucin and Ø14 - ** 14Cõdoxorubicin. This process is characterized in that the 9-deacetyl-9-formyl-N-trifluoroacetyl-daunorubicin is reacted, in solution in an aprotic organic solvent such as CH 2 Cl 2 or diethyl ether, at room temperature, for about 60 minutes under vacuum, with Ø14Cõ-diazomethane to form Ø14 - ** 14Cõ-N-trifluoroacetyl-daunorubicin, which is purified by column chromatography, or on plate, of silica-gel, then treated with a 0.1N aqueous solution of NaOH, or NH4 OH, a temperature of 0 to 5 degrees C for about 30 to 60 minutes, in order to hydrolyze the N-trifluoroacetyl protecting group ...

POLY-4-AMINOPYRROLE-2-CARBOXAMIDES AND DERIVATIVES, PROCESS FOR THEIR PREPARATION AND THEIR THERAPEUTIC USES

ANALOGUES OF DAUNORUBICIN AND DOXORUBICIN, PROCESS FOR THEIR PREPARATION AND USE THEREOF AS MEDICAMENTS

NOUVEAUX GLYCOSIDES D'ANTHRACYCLINE ANTITUMORAUX AYANT LA FORMULE GENERALEI SUIVANTE: (CF DESSIN DANS BOPI) DANS LAQUELLE X REPRESENTE UN ATOME D'HYDROGENE OU UN GROUPE HYDROXY, R REPRESENTE UN ATOME D'HYDROGENE OU UN GROUPE METHYLE, L'UN DE R ET R REPRESENTE UN GROUPE METHOXY ET L'AUTRE DE R ET R REPRESENTE UN ATOME D'HYDROGENE. CES COMPOSES ET LEURS SELS D'ADDITION ACIDE PHARMACEUTIQUEMENT ACCEPTABLES ONT UNE ACTIVITE ANTITUMORALE REMARQUABLE QUI LES REND UTILES COMME MEDICAMENTS. NEW ANTITUMORAL ANTHRACYCLINE GLYCOSIDES HAVING THE FOLLOWING GENERAL FORMULA: (CF DRAWING IN BOPI) IN WHICH X REPRESENTS A HYDROGEN ATOM OR A HYDROXY GROUP, R REPRESENTS A HYDROGEN ATOM AND A METHUN RYLE OR A GROUP R REPRESENTS A METHOXY GROUP AND THE OTHER OF R AND R REPRESENTS A HYDROGEN ATOM. THESE COMPOUNDS AND THEIR PHARMACEUTICALLY ACCEPTABLE ADDITIONAL SALTS HAVE REMARKABLE ANTI-TUMOR ACTIVITY WHICH MAKES THEM USEFUL AS MEDICINAL PRODUCTS.

Process for the preparation of 4'-deoxy-daunorubicin and 4'-deoxy-doxorubicin

ABSTRACT OF THE DISCLOSURE A new process for the preparation of the known 4'-deoxydaunorubicin and 4'-deoxydoxorubicin is disclosed. The used starting material is 4'-epi-N-trifluoroacetyldaunorubicin which is converted into 4'-deoxy-4'-iodo-N-trifluoroacetyl-daunorubicin from which 4'-deoxy-daunorubicin can be reductively obtained and eventually transform, by known methods, into 4'-deoxy-doxorubicin.

PROCESS FOR THE PREPARATION OF GLYCOSIDES DERIVED FROM OPTICALLY ACTIVE ANTHRACYCLINES

L'invention a pour objet un procédé de préparation d'anthracyclines glycosides. On prépare essentiellement les composés de formule I : The subject of the invention is a process for the preparation of anthracycline glycosides. The compounds of formula I are essentially prepared:

NEW ANTITUMOR GLYCOSIDES OF THE ANTHRACYCLINE SERIES AND PROCESS FOR THEIR PREPARATION

Patent FR2371461B1

NOVEL 4'-IODO DERIVATIVES OF ANTHRACYCLINE GLYCOSIDES AND THEIR USE AS A MEDICINAL PRODUCT

NOUVEAUX DERIVES 4-IODO DE GLYCOSIDES D'ANTHRACYCLINE ET LEUR EMPLOI COMME MEDICAMENT. COMPOSES GLYCOSIDIQUES D'ANTHRACYCLINE DE FORMULE GENERALE I: (CF DESSIN DANS BOPI) DANS LAQUELLE R EST UN ATOME D'HYDROGENE OU UN GROUPE HYDROXY, NOTAMMENT LA 4-DESOXY-4-IODODAUNORUBICINE ET LA 4-DESOXY-4-IODODOXORUBICINE QUI ONT UNE ACTIVITE ANTITUMORALE REMARQUABLE. NEW 4-IODO DERIVATIVES OF ANTHRACYCLINE GLYCOSIDES AND THEIR USE AS A MEDICINAL PRODUCT. GLYCOSIDIC COMPOUNDS OF ANTHRACYCLINE OF GENERAL FORMULA I: (CF DRAWING IN BOPI) IN WHICH R IS A HYDROGEN ATOM OR A HYDROXY GROUP, ESPECIALLY 4-DESOXY-4-IODODAUNORUBICIN AND 4-DESOXY-4TUB-IODICINEODOXY REMARKABLE ANTI-TUMOR ACTIVITY.

Process for Preparing Therapeutically Useful Poly-4-Aminopyrrol-2-Carboxamide Derivatives

Camptothecin derivatives and the use thereof as antitumor agents

Compounds of formula (I), wherein: R1 is -CN, -CH(CN)-R4, -CH=C(CN)-R4, -CH2-CH(CN)-R4, -C(=NOH)-NH2, -C(=NH)-NH2, -CH=C(NO2)-R4, -CH(CN)-R5, -CH(CH2NO2)-R5; 5-tetrazolyl, 2-(4,5-dihydrooxazolyl), 1,2,4-oxadiazolin-3-yl-5-one; R2 is hydrogen; R3 is hydrogen, OR6; R4 is hydrogen, C1-C6 linear or branched alkyl, CN, COOR7; R5 is hydrogen, OR8; R6 is hydrogen, C1-C6 linear or branched alkyl, (C6-C12) aryl (C1-C4) alkyl, (C1-C4) alkoxy (C1-C4) alkyl, (C1-C4) alkyl (C6-C12) aryl, (C6-C12) aryl (C2-C4) acyl, (C2-C4) acyl, amino (C1-C4) alkyl, amino (C2-C4) acyl, glycosyl; R7 is hydrogen, C1-C6 linear or branched alkyl, (C6-C12) aryl (C1-C4) alkyl, (C1-C4) alkoxy (C1-C4) alkyl, (C1-C4) alkyl (C6-C12) aryl; R8 has the same meanings of R6, independently of the latter. These compounds are active as topoisomerase I inhibitors and can be used as antitumor drugs.

Prep. of 6-deoxyanthracyclinones

METHOD OF ANALOGUE FOR THE PREPARATION OF 4'-EPI-DAUNOMYCINE OR ITS INDIVIDUAL ALFA OR BETA ANOMERS THEREOF

New anthracycline glycosides, method for preparing them and their application as antitumour agents

ANTHRACYCLINE GLYCOSIDES REPRESENTES PAR LES FORMULES GENERALES (I) ET (II): (CF DESSIN DANS BOPI) DANS LESQUELLES R REPRESENTE UN ATOME D'HYDROGENE OU UN GROUPE HYDROXYLE, ET LEURS SELS D'ADDITION AVEC UN ACIDE, QUI SONT PHARMACEUTIQUEMENT ACCEPTABLES. UTILISATION DE CES COMPOSES EN TANT QU'AGENTS ANTITUMORAUX. ANTHRACYCLINE GLYCOSIDES REPRESENTED BY THE GENERAL FORMULAS (I) AND (II): (CF DRAWING IN BOPI) IN WHICH R REPRESENTS A HYDROGEN ATOM OR A HYDROXYL GROUP, AND THEIR ADDITIONAL SALTS WITH AN ACID, WHICH ARE PHARMACEUTICALLY ACID. USE OF THESE COMPOUNDS AS ANTITUMOR AGENTS.

Poly-4-aminopyrrole-2-carboxamido derivatives and their use as site specific alkylating agents

A B S T R A C T The invention relates to distamycin A analogs of the following formula wherein n is 2, 3 or 4; A is an optionally substituted diva-lent radical chosen from , , and -Het- wherein Het is a pentatomic or hexatomic heteromono-cyclic ring, except pyrrole; and wherein either one of R1 and R2 is hydrogen and the other is an acylating moiety or R1 and R2 are both hydrogen or both alkyl groups optionally substitu-ted, including the pharmaceutically acceptable salts of the said compounds. The compounds of the invention can be useful antitumor and antiviral agents.

4'-IODODERIVATES OF ANTHRACYCLINONIC GLYCOSIDES.

Novel dual targeting antitumoural conjugates

The present invention relates to dual-targeting cytotoxic compounds of formula (I) and to their preparation. The described compounds are endowed with tumour specific action, incorporating three functional units: a tumour recognition moiety and a tumour selective enzymatic substrate sequence connected together by means of a spacer. These conjugates are designed to guarantee serum stability and, at the same time, the desired action inside the tumour cells as a result of enzymatic cleavability. [(L-L--D)m-E]m F-D-PI-SI-CT Formula (I).

ANALOGY PROCEDURE FOR PREPARING DAUNORUBICIN AND DOXORUBICIN ANALOGUE

Camptothecin derivatives conjugated in position 20 with integrin antagonists

Process for the preparation of 4'-epidaunorubicin, 3',4'-diepidaunorubicin, intermediates created thereby, as well as their use

Camptothecin derivatives process for their preparation, use thereof as antitumor agents and pharmaceutical compositions containing them

A találmány (I) általánős képletű új vegyületekre - a képletben R1 jelentése -CN, -CH(CN)-R4, -CH=C(CN)-R4, -CH2-CH(CN)-R4, -C(=NOH)-NH2, -C(=NH)-NH2, -CH=C(NO2)-R4, -CH(CN)-R5, -CH(CH2NO2)-R5; 5-tetrazőlil-csőpőrt, 2-(4,5-dihidrőxi-őxazőlil)-csőpőrt, 1,2,4-őxadiazőlin-5-őxő-3-il-csőpőrt; R2 jelentése hidrőgénatőm; R3 jelentése hidrőgénatőm vagy OR6; R4 jelentése hidrőgénatőm, 1-6 szénatőmős egyenes vagy elágazószénláncú alkilcsőpőrt, CN vagy COOR7; R5 jelentése hidrőgénatőm vagy OR8; R6 jelentése hidrőgénatőm, 1-6 szénatőmős egyenes vagy elágazószénláncú alkilcsőpőrt, (6-12 szénatőmős aril)-(1-4 szénatőmős alkil)-csőpőrt, (1-4 szénatőmős alkőxi)-(1-4 szénatőmős alkil)-csőpőrt, (1-4szénatőmős alkil)-(6-12 szénatőmős aril)-csőpőrt, (6-12 szénatőmősaril)-(2-4 szénatőmős acil)-csőpőrt, 2-4 szénatőmős acilcsőpőrt,aminő-(1-4 szénatőmős alkil)-csőpőrt, aminő-(2-4 szénatőmős acil)-csőpőrt, glikőzilcsőpőrt; R7 jelentése hidrőgénatőm, 1-6 szénatőmős egyenes vagy elágazószénláncú alkilcsőpőrt, (6-12 szénatőmős aril)-(1-4 szénatőmős alkil)-csőpőrt, (1-4 szénatőmős alkőxi)-(1-4 szénatőmős alkil)-csőpőrt, (1-4szénatőmős -alkil)-(6-12 szénatőmős aril)-csőpőrt; R8 jelentése valamely, az R6 jelentésére megadőtt csőpőrt, R6jelentésétől függetlenül - valamint N1-őxidjaikra, izőmerjeikre,diasztereőizőmerjeikre, enantiőmerjeikre és ezek elegyeire, valamintaktív metabőlitjaikra vőnatkőzik. A fenti vegyületek tőpőizőmeráz Iinhibitőrők, fenti hatásűk következtében tűmőrellenes aktivitásúgyógyszerként alkalmazhatók. A találmány tárgyát képezi az (I)általánős képletű vegyületek előállítására szőlgáló eljárás és azezeket tartalmazó gyógyszerkészítmények is. ŕ The present invention provides novel compounds of formula (I) wherein R1 is -CN, -CH (CN) -R4, -CH = C (CN) -R4, -CH2-CH (CN) -R4, -C (= NOH ) -NH 2, -C (= NH) -NH 2, -CH = C (NO 2) -R 4, -CH (CN) -R 5, -CH (CH 2 NO 2) -R 5; 5-tetrazolyl tube, 2- (4,5-dihydroxyhexazolyl) tube, 1,2,4-oxadiazoline-5-oxo-3-yl tube; R2 is hydrogen; R3 is ...

Camptothecin derivatives and the use thereof as antitumor agents

PCT No. PCT/EP97/00786 Sec. 371 Date Aug. 20, 1998 Sec. 102(e) Date Aug. 20, 1998 PCT Filed Feb. 19, 1997 PCT Pub. No. WO97/31003 PCT Pub. Date Aug. 28, 199720S-Camptothecin derivatives in which the 7-position bears as a substituent -CN, -CH(CN)R4, -CH=C(CN)R4, -C(=NOH)NH2, -C(=NH)NH2, -CH=C(NO2)R4, -CH(CN)R5, -CH(CH2NO2)R5, tetrazol-5-yl, 4,5-dihydrooxazol-2-yl, or 1,2,4-oxadiazolin-3-yl-5-one. These compounds are active as topoisomerase I inhibitors, and can be used as antitumor drugs.

ANTHRACYCLINE GLYCOSIDES, METHOD FOR THE PRODUCTION THEREOF AND MEDICINAL PRODUCTS CONTAINING THESE COMPOUNDS

7-t-butoxyiminomethylcamptothecin conjugated in position 20 with integrin antagonists

Compounds of Formula (I) are described; in which the R1 group is as defined in the specification and includes the condensation of 7-t-butoxyiminomethylcamptothecin in position 20 with a cyclopeptide containing the RGD sequence. Said compounds are endowed both with high affinity for integrin receptors .alpha.v.beta.3 and .alpha.v.beta.5 and with selective cytotoxic activity on human tumour cell lines at micromolar concentrations.

Process for the preparation of 4-demethoxydaunomycinone

6-deoxyanthracyclinones

Novel dual targeting antitumoural conjugates

The present invention relates to dual-targeting cytotoxic compounds of formula (I) and to their preparation. The described compounds are endowed with tumour specific action, incorporating three functional units: a tumour recognition moiety and a tumour selective enzymatic substrate sequence connected together by means of a spacer. These conjugates are designed to guarantee serum stability and, at the same time, the desired action inside the tumour cells as a result of enzymatic cleavability. [(L-D) n E] m -F-D-PI-SI-CT Formula (I).

Derivatives of totally n-desulphated glycosaminoglycans as heparanase inhibitors, endowed with antiangiogenic activity and devoid of anticoagulating effect

ANTHRACYCLINONIC GLUCOSIDES

ANTHRACYCLING GYCOSIDES, THEIR MANUFACTURING, INTERMEDIATES THEREOF, AND PREPARATIONS CONTAINING THESE AND THEIR USE

Pyrrole-2-carboxamido-propionamidines

9-Amino and 9-nitro-camptothecin Derivatives, Methods for their Preparation and Use as Antitumor Agents

Camptothecins conjugated in position 7 with integr

NYA ANTRACYKLINER.

METHOD FOR PRODUCING NEW 4'-HALOGENANTHRACYCLINGLYCOSIDES

Epi-daunomycin and epi-adriamycin compounds and method of use

Disclosed is a process for preparing glycoside antitumor antibiotics, including the known compounds daunomycin, adriamycin, 4'-epi-daunomycin and 4'-epi-adriamycin and the novel antibiotics, 3',4'-epi-6'-hydroxydaunomycin, 3',4'-epi-6'-hydroxyadriamycin. 3',4'-epi-daunomycin, 3',4'-epi-adriamycin, 4-demethoxy-4'-epi-daunomycin and 4-demethoxy-4'-epi-adriamycin. Process involves reacting daunomycinone or 4-demethoxy-daunomycinone with a protected 1-halo derivative of 3,4-epi-6-hydroxydaunosamine, 3,4-epi-daunosamine or 4-epi-daunosamine in an inert solvent in the presence of a soluble silver salt catalyst to form a protected derivative of the glycoside antibiotic and removing the protecting groups.

Retinoid derivatives with antiangiogenic, antitumoral and proapoptotic activities

Are described compounds of Formula (I) in which R, R', R'', A, and D have the meanings described in the text, as useful agents in the cure of pathologies characterised by altered angiogenesis and as antitumorals.

Antitumor anthracycline glycosides, their preparation, intermediates thereof, and compositions and use thereof

ABSTRACT ANTITUMOR ANTHRACYCLINE GLYCOSIDES, THEIR PREPARATION, INTERMEDIATES THEREOF AND COMPOSITIONS AND USE THEREOF New anthracycline glycosides having formula:

Industrial process for the preparation of l-carnitine

The present invention describes a process for the industrial production of L - carnitine, comprising the enantioselective reduction of an alkyl 4-chloro-3- oxobutyrate or 4-chloro-3-oxobutyramide. The optically active 3-hydroxy derivative thus obtained is reacted with trimethylamine, obtaining crude L- carnitine, which is then finally purified. The catalyst used for the reducti on is a complex of ruthenium bound to a penta-atomic bis-heteroaromatic system. The reduction reaction, performed in controlled conditions of hydrogen pressure, substrate concentration, temperature, and substrate: catalyst mola r ratio, enables 4-chloro-3-hydroxybutyrate or 4-chloro-hydroxybutyramide to b e obtained in a high yield. The process described, which leads to L-carnitine being obtained, is easily applicable on an industrial scale.

DERIVATIVE FROM CAMPTOTECHINE THAT HAVE ANTI-TUMOR ACTIVITY

SE REFIERE A COMPUESTOS DERIVADOS DE CAMPTOTECINA DE FORMULA I, DONDE R1 ES C(R5)=N-O(n)R4; R4 ES H, ALQUILO C1-C8, ALQUENILO C1-C8, CICLOALQUILO C3-C10, CICLOALQUILO C3-C10-ALQUILO C1-C8, ARILO C6-C14, HETEROCICLO, HETEROCICLO-ALQUILO C1-C8, ENTRE OTROS; R4 ES AROILO C6-C10, ARILSULFONILO C6-C10 OPCIONALMENTE SUSTITUIDO CON HALOGENO, OH, ALQUILO C1-C8, ALCOXI, FENILO, CIANO, NITRO, NR10R11; R10 Y R11 SON H, ALQUILO C1-C8; R4 ES POLIAMINOALQUILO, GLICOSILO; n ES 0-1; R5 ES H, ALQUILO C1-C8, ALQUENILO C1-C8, CICLOALQUILO C3-C10, CICLOALQUILO C3-C10-ALQUILO C1-C8, ENTRE OTROS; R2 Y R3 SON H, OH, ALCOXI C1-C8, CUANDO R5, R2 Y R3 SON H; n ES 1, ENTONCES R4 NO ES H. SON COMPUESTOS PREFERIDOS 7-METOXIIMINOMETILCAMPTOTECINA, 7-METOXIIMINOMETILO-10-HIDROXICAMPTOTECINA, 7-[N-(4-AMINOBUTILO)-2-AMINOETOXI]IMINOMETILCAMPTOTECINA, ENTRE OTROS. TAMBIEN SE REFIERE A UN PROCEDIMIENTO PARA LA PREPARACION, A COMPUESTOS INTERMEDIOS Y A UNA COMPOSICION FARMACEUTICA QUE COMPRENDE ADEMAS UN AGENTE ANTITUMORAL. EL COMPUESTO I PUEDE SER UTIL PARA EL TRATAMIENTO DE TUMORES, INFECCIONES VIRALES, ACTIVIDAD ANTIPLASMODIO FALCIPARUM REFERS TO CAMPTOTECHIN-DERIVED COMPOUNDS OF FORMULA I, WHERE R1 IS C (R5) = N-O (n) R4; R4 IS H, C1-C8 ALKYL, C1-C8 ALKENYL, C3-C10 CYCLOALKYL, C3-C10 CYCLOALKYL-C1-C8 ALKYL, C6-C14 ARYL, HETEROCYCLE, C1-C8 HETEROCYCLE-ALKYL, AMONG OTHERS; R4 IS C6-C10 AROYL, C6-C10 ARYLSULFONYL OPTIONALLY SUBSTITUTED WITH HALOGEN, OH, C1-C8 ALKYL, ALCOXY, PHENYL, CYANE, NITRO, NR10R11; R10 AND R11 ARE H, C1-C8 ALKYL; R4 IS POLYAMINEALKYL, GLYCOSIL; n IS 0-1; R5 IS H, C1-C8 ALKYL, C1-C8 ALKENYL, C3-C10 CYCLOALKYL, C3-C10 CYCLOALKYL-C1-C8 ALKYL, AMONG OTHERS; R2 AND R3 ARE H, OH, C1-C8 ALCOXY, WHEN R5, R2 AND R3 ARE H; n IS 1, THEN R4 IS NOT H. PREFERRED COMPOUNDS 7-METOXYIMINOMETHYLCAMPTOTHYCINE, 7-METHOXYIMINOMETHYL-10-HYDROXYCAMPTOTHYLINE, 7- [N- (4-AMINOBUTYL) -2-AMINOETOXY] IMINTROMETILCAMPTOTHYCINE, ENAMPTOTHETIC. IT ALSO REFERS TO A PROCEDURE FOR THE PREPARATION, TO ...

Daunorubicin derivatives, their preparation and their use

Daunorubicin (also known as daunomycin) derivatives of the formula ##STR1## wherein X is ##STR2## and R is --COCF 3 or H which are prepared by hydrogenating 9-desacetyl-9-keto-N-trifluoroacetyldaunorubicin, an unexpectedly stable key-intermediate which is itself a new compound, are useful in treating certain mammalian tumors.

Novel morpholine derivatives of daunorubicine and doxorubicine

Anthracycline glycosides of the general formula (A): <IMAGE> (A) wherein X is hydrogen or hydroxy and R is hydrogen or a methyl or a hydroxymethyl group; and their pharmaceutically acceptable salts; are useful as antitumor agents.

Process for the production of new pyrrole derivatives

Process for the production of 4-substituted anthracyclinones and anthracyclinglycosides

4-substituted anthracyclinones of formula (I) <CHEM> wherein R represents a hydrogen atom or a straight or branched alkyl, alkenyl or alkynyl group having from 1 to 10 carbon atoms, are intermediates in the preparation of antitumor anthracycline glycosides of formula (IX): <CHEM> wherein R is as defined above and R1 is a hydrogen atom or a hydroxy group, and pharmaceutically acceptable salts thereof.

New antitumor anthracyclines

Anthracycline glycosides of general formula (I) wherein R is hydrogen or hydroxy, and pharmaceutically acceptable slats thereof, are anti-tumor agents.

Camptothecins conjugated in position 7 to cyclic peptides as cytostatic agents

Spojevi formule (I) ,u kojima: i je 0 ili 1; R1 je skupina -CH=N-(O)m-R2-Z-X-Y; gdje m je 0 ili 1; R2 je odabran iz skupine koju sačinjavaju linearni ili razgranati C1-C7 alkilen, linearni ili razgranati C2-C7 alkenilen, C3-C10 cikloalkilen, C3-C10 cikloalkenilen, C6-C14 arilen, arilen (C6-C14)-alkilen (C1-C6), alkilen (C1-C6)-arilen (C6-C14), aromatski ili nearomatski heterocikl (C3-C14), koji sadržava najmanje jedan heteroatom odabran iz skupine koju sačinjavaju O, N, S; heterocikloalkilen (C3-C10) alkilen (C1-C6) koji sadržava najmanje jedan heteroatom odabran iz skupine koju sačinjavaju O, N, S; alkilen (C1-C6)-heterocikloalkilen (C3-C10) koji sadržava najmanje jedan heteroatom odabran iz skupine koju sačinjavaju O, N, S); poliaminoalkil skupina formule -(CH2)m1-NR8-(CH2)n1-NR9-(CH2-CH2-CH2-NR9)p1-H, gdje m1 i n1, koji mogu biti jednaki ili različiti, su cijeli broj od 2 do 6 i p1 je cijeli broj od 0 do 3; R8 i R9, koji mogu biti jednaki ili različiti, su odabrani iz skupine koju sačinjavaju H, linearni ili razgranati C1-C6 alkil, Boc, Cbz; monosaharidi, kao što je 6-D-galaktozil, ili 6-D-glukozil; svaka od gore navedenih skupina može po potrebi biti supstituirana s jednom ili više skupina odabranih iz skupine koju sačinjavaju CN, NO2, NH2, OH, SH, COOH, COO-(alkil)(C1-C5), CONH-(alkil)(C1-C5), SO3H, SO3-(alkil)(C1-C5), pritom alkil skupina je linearna ili razgranata; atom halogena; Z je ili odsutan, ili odabran od -NH-, -CO-, -O-;X je ili odsutan, ili je odabran iz skupine koju sačinjavaju -COCHR3NH-, -COCHR6(CH2)n2R4-, -R4-CH2 (OCH2CH2)n3OCH2R4-, -R4(Q)R4-, -R5[Arg-NH(CH2)n1CO]n4R5-, -R5-[N-gvanidinopropil-Gly]n3R5-, -CON [CH2)n4NHR7]CH2-, u kojoj n1 je cijeli broj od 2 do 6, n2 je cijeli broj od 0 do 5, n3 je cijeli broj od 0 do 50, n4 je cijeli broj od 2 do 7; R3 je H ili linearni ili razgranati C1-C4 alkil, po potrebi supstituiran s -COOH, - CONH2, -NH2 ili -OH; C6-C14 aril; R4 je odabran iz skupine koju sačinjavaju: -NH-, -CO-, -CONH-, -NHCO-;R5 je ili ...

4-SUBSTITUTED ANTHRACYCLINONES AND ANTHRACYCLING LYCOSIDES, AND THEIR PREPARATION

CAMPTOTECIN DERIVATIVES AND THEIR USE AS ANTI-CANCER AGENTS

METHOD FOR PREPARING NEW GLYCOSIDIC DERIVATIVES OF ANTRACYCIN AND OF PHARMACEUTICAL COMPOSITIONS CONTAINING THEM

10-Noranthracyclines

METHOD FOR PRODUCING NEW ANTHRACYCLINGLYCOSIDES

4-substituted anthracyclinones and anthracycline glycosides and their preparation

4-substituted anthracyclinones of formula (I) <CHEM> wherein R represents a hydrogen atom or a straight or branched alkyl, alkenyl or alkynyl group having from 1 to 10 carbon atoms, are intermediates in the preparation of antitumor anthracycline glycosides of formula (IX): <CHEM> wherein R is as defined above and R1 is a hydrogen atom or a hydroxy group, and pharmaceutically acceptable salts thereof.

Patent GR77890B

4-demethoxy-4-carboxy-daunomycinone ester derivatives, pharmaceutical compositions and preparatory processes

4-substituted anthracyclinones of formula (I) <CHEM> wherein R represents a hydrogen atom or a straight or branched alkyl, alkenyl or alkynyl group having from 1 to 10 carbon atoms, are intermediates in the preparation of antitumor anthracycline glycosides of formula (IX): <CHEM> wherein R is as defined above and R1 is a hydrogen atom or a hydroxy group, and pharmaceutically acceptable salts thereof.

Substituted camptothecin derivatives and process for their preparation

PROCEDURE FOR PREPARING POLY-4-AMINOPYRROLE-2-CARBOXAMIDODE DERIVATIVES.

FREQUENCY REFRIGERATION OF 4'-DEOXIDOXICUBE OCH 4'-DEOXIDOXORUBIC

Process for the preparation of antitumor anthracycline glycosides, their intermediates and compositions and use thereof

ABSTRACT OF THF DISCLOSURE A process for the preparation of novel antitumor an-thracycline glycosides by condensing daunomycinone wlth 2,3,4,6-tetradeoxy-4-C-methylene-3-trifluoroacetamido-L-threo-hexopyranosyl chloride; 2,3,4,6-tetradeoxy-4-C-methylene-3-trifluoroacetamido-L-arabino-hexopyranosyl chloride or 2,3,6-trideoxy-4-C-trifluoro-acetamideomethyl-3-trifluoroacetamido-3-0-trifluoroacetyl-L-lyxo-hexopyranosyl chloride.

METHOD FOR PRODUCING ANTHRACYCLINGLYCOSIDES

Campothecin derivatives of antitumour effect

Oписват се производни на камптотецин от формула (I), където групите R1 R2 и R3 са както е дефинирано в описанието. Съединенията от формула (I) имат антитуморно действие и показват добър терапевтичениндекс. Описани са също методи за получаването насъединенията от формула (I) и тяхното приложение при приготвянето на медикаменти, полезни при лечението на тумори, вирусни инфекции и инфекции с plasmodium falciparum.

Process for producing poly-/4-amino-pyrrolo-2-carboxamido/derivatives

4'-epi-Daunomycins, their preparation and pharmaceutical compositions containing these compounds

NITROANTHRACYCLINE, METHOD FOR THE PRODUCTION THEREOF, AND MEDICINAL PRODUCTS CONTAINING THEM

NEW ANTITUMOR DEOXYANTRACYCLINES.

4-substituted anthracyclinones and anthracycline glycosides and their preparation

4-substituted anthracyclinones of formula (I) <CHEM> wherein R represents a hydrogen atom or a straight or branched alkyl, alkenyl or alkynyl group having from 1 to 10 carbon atoms, are intermediates in the preparation of antitumor anthracycline glycosides of formula (IX): <CHEM> wherein R is as defined above and R1 is a hydrogen atom or a hydroxy group, and pharmaceutically acceptable salts thereof.

Derivatives of partially desulphated glycosaminoglycans endowed with antiangiogenic activity and devoid of anticoagulating effect

Derivatives of partially desulphated glycosaminoglycans endowed with antiangiogenic activity and devoid of anticoagulating effect

Process for the preparation of new anthracyclines

4'-epi-Adriamycin α and β anomer, process for their preparation and pharmaceutical compositions containing them

Beta- {1-methyl-4- [1-methyl-4- (1-methyl-4-formylamino-pyrrole-2-carboxamido) -pyrrole-2-carboxamido] -pyrrole-2-carboxamido} -propionamidine and its acid addition salts

Anthracyclines

ABSTRACT OF THE DISCLOSURE This invention discloses a process for producing 9-desacetyl-9-keto-N-trifluoroacetyl-daunorubicin and the compound itself. The process comprises oxidizing N-trifluoro-acetyl-13-dihydrodaunorubicin in t-butyl alcohol in the presence of two equivalents of sodium periodate. These compounds are unexpectedly stable intermediates useful in the production of new daunorubicin derivatives which are used in treating certain mammalian tumours.

METHOD OF PREPARING 4'-EPIDAUNORUBICIN AND 3 ', 4'-DIEPIDAUNORUBICIN

FRAME STEERING ANALOGGER, FRAME FRAME STEERING

Derivatives of partially desulphated glycosaminoglycans endowed with antiangiogenic activity and devoid of anticoagulating effect

Partially desulphated glycosaminoglycan derivatives are described, particularly heparin, and more particularly formula (I) compounds, where the U, R and R1 groups have the meanings indicated in the description. Said glycosaminoglycan derivatives are endowed with antiangiogenic activity and a re devoid of anticoagulant activity.

Chiral synthesis of anthracyclines from substituted anthraquinones

Anthracycline glycosides of formula (I): ##STR1## wherein R 1 and R 2 are independently selected from hydrogen, methyl, ethyl or methoxy and pharmaceutically acceptable acid addition salts thereof, which are useful in treatment of human cancer, are prepared by a stereospecific condensation of a derivative of daunosamine of general formula (II): ##STR2## wherein R 3 is an alkyl, perfluoroalkyl or aryl group and R 4 , R 5 , R 6 and R 7 are independently selected from alkyl, aryl or aralkyl having up to ten carbon atoms, with a quinone quinizarine epoxide of general formula (III) ##STR3## and conversion of the product obtained to the anthracycline glycoside of formula (I) or salt thereof.

Water-soluble camptothecin derivatives, process for their preparation and their use as antitumor agents

Substituted camptothecin derivatives and process for its preparation

NEW SUBSTITUTED ANTITUMORANTHRACYCLINE AND METHOD FOR THE PRODUCTION THEREOF

Water-soluble camptothecin derivatives, process for their preparation and their use as antitumor agents

Daunorubicin and doxorubicin analogues, their preparation and use thereof

ABSTRACT OF THE DISCLOSURE New antitumor anthracycline glycosides are disclosed, having the general formula I:

Bis-heterocyclic compounds with antitumour and chemosensitising activity

Bis-heterocyclic compounds of general formula (I) are described which are useful as antitumour and cheomsensitising agents.

Adriamycins and uses thereof

The known antitumor antibiotic adriamycin and its β-anomer, and the novel compounds, 4'-epiadriamycin (both α- and β-anomers) are prepared by condensing a novel, reactive protected derivative of adriamycinone with reactive intermediates which are 1-halo-2,3,6-trideoxy-3-trifluoroacetamido-4-trifluoroacetoxy-α-L-lyxo (or arabino) hexopyranoses.